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61.
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64.
  • Fratzl-Zelman, N., et al. (författare)
  • Bone material properties and response to teriparatide in osteoporosis due to WNT1 and PLS3 mutations
  • 2021
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with osteoporosis-associated WNT1 or PLS3 mutations have unique bone histomorphometric features and osteocyte-specific hormone expression patterns. Objective: To investigate the effects of WNT1 and PLS3 mutations on bone material properties. Design: Transiliac bone biopsies were evaluated by quantitative backscattered electron imaging, immunohistochemistry, and bone histomorphometry. Setting: Ambulatory patients. Patients: Three pediatric and eight adult patients with WNT1 or PLS3 mutations. Intervention: Bone mineralization density distribution and osteocyte protein expression was evaluated in 11 patients and repeated in six patients who underwent repeat biopsy after 24 months of teriparatide treatment. Main outcome measure: Bone mineralization density distribution and protein expression. Results: Children with WNT1 or PLS3 mutations had heterogeneous bone matrix mineralization, consistent with bone modeling during growth. Bone matrix mineralization was homogenous in adults and increased throughout the age spectrum. Teriparatide had very little effect on matrix mineralization or bone formation in patients with WNT1 or PLS3 mutations. However, teriparatide decreased trabecular osteocyte lacunae size and increased trabecular bone FGF23 expression. Conclusion: The contrast between preserved bone formation with heterogeneous mineralization in children and low bone turnover with homogenous bone mineral content in adults suggests that WNT1 and PLS3 have differential effects on bone modeling and remodeling. The lack of change in matrix mineralization in response to teriparatide, despite clear changes in osteocyte lacunae size and protein expression, suggests that altered WNT1 and PLS3 expression may interfere with coupling of osteocyte, osteoblast, and osteoclast function. Further studies are warranted to determine the mechanism of these changes.
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65.
  • Frysz, Monika, et al. (författare)
  • The influence of adult hip shape genetic variants on adolescent hip shape : Findings from a population-based DXA study
  • 2021
  • Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 143
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape.Methods: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2.Results: Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta -0.05, p = 9.9 x 10(-8); age 18: -0.05, p = 3.3 x 10(-6)) and HSM5 (age 14: beta -0.07, p = 1.6 x 10(-4); age 18: -0.1, p = 2.7 x 10(-6)). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 x 10(-5); age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: -0.06, p = 0.001; age 18: -0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture.Conclusion: In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life.
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66.
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67.
  • Gatenholm, Birgitta, 1986, et al. (författare)
  • Spatially matching morphometric assessment of cartilage and subchondral bone in osteoarthritic human knee joint with micro-computed tomography
  • 2019
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 120, s. 393-402
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Objective: The objective of this study was to develop a reproducible and semi-automatic method based on micro computed tomography (microCT) to analyze cartilage and bone morphology of human osteoarthritic knee joints in spatially matching regions of interest. Materials and methods: Tibial plateaus from randomly selected patients with advanced osteoarthritis (OA) who underwent total knee arthroplasty surgery were microCT scanned once fresh and once after staining with Hexabrix. The articular surface was determined manually in the first scan. Total articular surface, defect surface and cartilage surface were computed by triangulation of the cartilage surface and the spatially corresponding subchondral bone regions were automatically generated and the standard cortical bone and trabecular bone morphometric indices were computed. Results: The method to identify cartilage surface and defects was successfully validated against photographic examinations. The microCT measurements of the cartilage defect were also verified by conventional histopathology using safranin O–stained sections. Cartilage thickness and volume was significantly lower for OA condyle compared with healthy condyle. Bone fraction, bone tissue mineral density, cortical density and trabecular thickness differed significantly depending on the level of cartilage damage. Conclusion: This new microCT imaging workflow can be used for reproducible quantitative evaluation of articular cartilage damage and the associated changes in subchondral bone morphology in osteoarthritic joints with a relatively high throughput compared to manual contouring. This methodology can be applied to gain better understanding of the OA disease progress in large cohorts.
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68.
  • Geraets, Wil G, et al. (författare)
  • Prediction of bone mineral density with dental radiographs
  • 2007
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 40:5, s. 1217-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • There is consensus to use the bone mineral density (BMD) for the operational definition of the degree of osteoporosis and the risk of osteoporotic fractures. Dual X-ray absorptiometry (DXA) is the common technique to determine BMD. Because of high costs and limited availability of DXA equipment it is worthwhile to look for alternative diagnostic techniques. As part of a larger study, the Osteodent project, we investigated if the trabecular pattern on dental radiographs can be used to predict BMD and to identify the subjects with osteoporosis and increased risk of osteoporotic fractures. In four clinical centers 671 women with an average age of 55 years were recruited. BMD values were measured by DXA equipment at the femoral neck, total hip, and spine. One panoramic and two intraoral radiographs were made. From 525 women a complete set of BMD values and radiographs was obtained. Four regions of interest on the radiographs were selected manually and then processed automatically. On all regions of interest mean and standard deviation of the gray values were measured and several features describing the shape of the binarized trabecular pattern. Multiple regression was used to predict BMD of total hip and spine by means of the radiographic measurements combined with age. It was found that age accounts for 10% of the variation in total hip BMD and 14% of the variation in spinal BMD. When all measurements on the dental radiographs are used the explained variation increases to 22% and 23%. The areas under the ROC curves are comparable to those of commonly used screening instruments for osteoporosis. It is concluded that prediction of DXA measurements of BMD by means of quantitative analysis of the trabecular pattern on dental radiographs is feasible. PMID: 17317351 [PubMed - indexed for MEDLINE]
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69.
  • Goldhahn, Jörg, et al. (författare)
  • Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:2, s. 343-347
  • Tidskriftsartikel (refereegranskat)abstract
    • Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. © 2008 Elsevier Inc. All rights reserved.
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70.
  • Goldhahn, Joerg, et al. (författare)
  • Evidence for anti-osteoporosis therapy in acute fracture situations-Recommendations of a multidisciplinary workshop of the International Society for Fracture Repair
  • 2010
  • Ingår i: BONE. - : Elsevier BV. - 8756-3282. ; 46:2, s. 267-271
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Society for Fracture Repair convened a multidisciplinary workshop to assess the current evidence around the interaction between anti-osteoporosis drugs and the healing of incident fractures, with a view to making recommendations for clinical practice. The consensus was that there is no evidence-based reason to withhold anti-resorptive therapy while a fracture heals, whether or not the patient was taking such therapy when the fracture occurred. The workshop also considered existing models of service provision for secondary prevention and concluded that the essential ingredient for reliable delivery is the inclusion of a dedicated coordinator role. Several unresolved issues were defined as subjects for further research, including the question of whether continuous long-term administration of anti-resorptives may impair bone quality. The rapidly changing area requires re-assessment of drugs and their interaction with fracture healing in the near future.
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